Abstract: Obesity is linked to chronic inflammation in white adipose tissue (WAT) which is exacerbated by infiltrating macrophages (MΦ)s. Grape powder extract (GPE) contains polyphenols that have the potential to prevent this inflammatory response that can otherwise lead to insulin resistance. Therefore, this research examined the extent to which GPE prevents lipopolysaccharide (LPS)-induced inflammatory response in human MΦs. Pretreatment of human MΦs with GPE prevented LPS-mediated activation of mitogen activated protein kinases (MAPK)s, nuclear factor kappa B (NFκ B), and activator protein (AP)-1, and induction of inflammatory genes. Furthermore, GPE decreased the capacity of LPS-stimulated MΦs to inflame adipocytes and cause insulin resistance. My preliminary data show that in the absence of LPS, quercetin (QUE), a polyphenol abundantly found in GPE, attenuated inflammatory gene expression, c-Jun N-terminal kinase (JNK) and c-Jun activation, and Iκ B α degradation in human MΦs. In addition, QUE pretreatment of MΦs prevented insulin resistance in human adipocytes exposed to MΦ-CM. Taken together, these data show that polyphenol-rich GPE decreases inflammation in human MΦs and MΦ-mediated insulin resistance in human adipocytes. Lastly, these data suggest that QUE may be one of the polyphenols in GPE that decrease inflammation and insulin resistance in human MΦs and adipocytes.